Lovastatin is, chemically [1S-[1.alpha.(R*),3.alpha., 7.beta., 8.beta.(2*, 4S*), 8.alpha..beta.]]-2-methylbutanoic acid 1,2,3,7,8,8.alpha.-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo -2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, and has the chemical formula: ##STR1##
It is useful as an antihypercholesterolemic, being a potent inhibitor of HMG-CoA reductase, the rate controlling enzyme in cholesterol biosynthesis. It is a fungal metabolite produced by fermentation processes using selected fungal strains.
Antibiotics such as lovastatin are metabolites which require sets of several enzymes for their synthesis. To permit their production by molecular cloning of antibiotic-producing microorganisms requires the isolation, analysis and, perhaps modification of the corresponding genes for the several enzymes. Attempts to isolate such genes from such fungal species have so far yielded clones carrying either individual genes of the set, or only incomplete gene sets - see Malpartida and Hopwood, "Molecular Cloning of the Whole Biosynthetic Pathway of a Streptomyces Antibiotic and its Expression in a Heterologous Host", Nature (1984), 309 pp 462-464.